Nonbenzenoid fused polycyclic compounds



Patented Oct. 30, 1945 2,387,830

UNITED STATES PATENT OFFICE' NONBENZENOID FUSED POLYCYCLIC COMPOUNDS Lewis W. Butz, Beltsville, M11, asslgnor to Claude R. Wickard, as Secretary of Agriculture of the Unltfleid States of Amerlca, and his successors in cc No Drawing. Application December 12, 1942, Serial No. 468,795

10 Claims. (Cl. 260239.5) I

(Granted under the act of March 3, 1883, as amended April 30, 1928; 370 0. G. 757) This application is made under the act of four rings of carbon atoms having substantially March 3, 1883, as amended by the act of April 30, the structure:

1928, and the invention herein described and claimed, if patented, may be manufactured and 1 H used by or for the Government of the United 5 States for governmental purposes without the 0H0B1 payment to me of any royalty thereon. c B, This is a continuation in part of my copendlns on, o c c I application for patent, Serial No. 362,420, filed October 23, 1940. E Q

My invention relates to non-benzenoid fused 0Q, on 00 polycyclic organic compounds and to processes for preparing them. o

I have found that organic compounds belongmg to the class of 1,5 d1ene 3 ynes, i. e" This is a. non-benzenoui steroid. It possesses pound containing th atomic grouping the seventeen-carbon four-ring skeleton common to all the steroids which have been found in organic materials. Furthermore, it is a steroid containing only hydrogenated rings and one novel feature of the process is its capacity to yield polycyclic compounds lacking any aromatic react with two moles of dienophilic compounds (b enzen 01 d) ring.

containing the atomic grouping All known processes for the synthesis of steroids relate to the preparation of benzenoid steroids. But the majority of the naturally occurring steroids, among them the therapeutically imsuch male anhydflde' methyl mmamte' ethyl DOrtant male hormones, adrenocortical hormones,

fumarate, and other maleates and fumarates inand progesterone are nonmenzenom.

eluding substituted compounds to form stable My process makes available, for the first time, addition products which contain two carbon rings by synthesis steroids of the nembenzenoid type morethan are containedmthedieneyne employed. as we as nomstemid types f polycyclic The reaction is rri d ou in the absence of y pounds, which are useful as intermediates in the solvent and at a temperature of 130 C. to 175 C. synthesis of therapeutic compounds,

The molecular weight of these products is equal My invention may be practiced by any of the to the sum of the molecular weight of the diprocedures illustrated in the following examples. eneyne employed and twice the molecular weight While I cite the use of a sealed glass tube, it is of the dienophilic compound used. to be understood that I may use any type of con- Thus the dieneyne, cyclohexenylcyclopentenyltainer that will permit the development of presacetylene sure during heating and that will exclude the 4.0 presence of atmospheric oxygen. I may use, also, K under certain conditions, any open type vessel,

CH O as illustrated by Example 5.

C Examle 1.1,5-Dimethyl-2,3,4,6,7,8-herahydr0- g E naphthalene 3,4,7,s tetracarboxylic 3,4,7,s-

g, n dianhydride One molecular proportion of 2,5-dimethyl-1,

5-hexadiene-3-yne (diisopropenylacetylene) was reacts readily with maleic anhydride. By this mixed with two molecular proportions of maleic reaction there is formed a compound containing anhydride and the mixture was heated, suitably in a sealed glass tube, at 130' C. for 1-5 hours. On cooling, with or without the addition of a solvent, such as acetone, ethyl acetate, or benzene, the product:

indicates that the two double bonds are at the positions shown in the structural formula. I

smmpze 2. m4) ,s-stemdm-amus-tem carbo ue-amuz-aaamdnde A mixture of one molecular proportion of cyclohexenylcyclopentenylacetylene and two molecular proportions of maleic aghydride was heated and the product was isolated as described in Example 1. The product, after purification, melts at about 249-251' C. when heated with pal-- ladium and charcoal it yields, among other-products, 16,16-dihydro-l'l-cyclopenta [a] phenanthrene. The carbon skeleton is thus demonstrated to be that foimd in the natural steroids. when heated with ethanol the product forms a monoethyl ester, CnHnOv, in good yield and a diethyl ester, CssHnOe in lesser yield. Free steradiene-6,7,11,12 tetracarboxylic acid, 'CuHaOs,

was isolated as in Example 1. The product mel at 250-259 (2., andhas the empiric composition CaaHnOe. It has substantially the structure:

The character of the ring system is demonstrated by the formation of the known substance chrysene by heating in the presence of platinized charcoal. Observation of the absorption spectrum indicates the presence of two conjugated double bonds spread over two rings. The product is further characterized by the fact that cis-6,7-cis-11,12-tetracarbory-8(14) ,9-

chrysitadiene, CaaHsaOe, can be prepared from the potassium'salt.This acid can be converted to a tetramethyl ester, CsaHaOl, by diasomethane, and the tetramethyl ester can be in acetic acid with Adams platinum oxide catalyst to form a dihydroester, CM.

sam le a-sa-uethvm,z,u,s,s,ss.1,8.a10,11,- IZJZa-tetradecahvdrochrusene-SJJIJz-tetrae rborullc-amisz-dwnhwanse One molecular proportion of -cyclohe'xenyl- (2- methylcyclohexenyl) -acetyiene and two molecular proportions of m'al'eic anh'ydride wereheated together andthe product was isolated as in Ex- I ample 1. The melting point of the pure product can be prepared by way of the potassium salt of the product. the free acid can be converted, to the tetramethyl ester, cannot, by diazomethane,

and the tetramethyl ester can be catalytically.

hydrogenated in acetic acid with Adams plati num oxide catalyst to form a dihydro ester, CzsHuOs. Analysis indicates the empiric composition to be CnHaoOe and the absorption spectrum is similar to that observed for the product described in Example 1. The probable structure of this product is, therefore, that'shown by the structural formula:

trample 3.-13,314,5,6,8a,7,8,9,10,11,12,12d-tetradecahudrochrvsene 5,6,11,12 tetracarbo:culic- 5,631,! Z-dianhfldride "is about z'nr-saoc. (in vacuum), the empiric formula is Cannon, and the structure is substan- The character of the ring system a by the formation of chrysene when the product a is heated in the presence of platinized charcoal.

Absorption spectrum data indicates the presence of two double bonds spread over two rinss.

trample s.'-1-'1 smnri- 5.6 mac-2,315,?

heechfldronaphthaleae-LL7J-tetracarboullc- 3,4;7, 8-dianhfldride I One molecular proportion of cyclopentenyl isopropenylacetylene was added to two molecular proportions of maleic anhydride in an openvessel at 120' C. while passinga stream of carbon dioxide to exclude air! The-mixture was heated at 1509-160 C. for two hours. Volatile compo- A preferable name for this product, though one not yet sanctioned by usage, employs the numbering' in use with steroids, viz., 8('14),9-chrysitadiene 6,7,l1,12-tetra carboxylic-6,'l,11,12-dianhydride.

One molecular proportion of dicyclohexenylacetylene and two molecular proportions of maleic anhydride were heated together and the product nents were then removed by fractional distilla Vtion. The residuewas dissolved in ethyl acetate and etherwas added, resultinz'infthe precipitation of an amorphous material. This amorphous material, was separated. Part of the ether and ethyl acetate was evaporated and .the solution was set aside to crystallize.

After seven days,

crystals formed which were separated and recrystallized from-benaene-petroleum ether. The

crystalline product is represented by the following structural formula:

CHrCHa The product has a melting point of 168-170 C. and its empiric composition is CnHuOc. The presence of two conjugated double bonds spread over two rings is substantiated by absorption spectrum data.

Example 6.-trans-6,7-trans-11,ZZ-Tetracarbomethorcy-8 (1 4) ,Q-chrysitadiene One molecular proportion of dicyclohexenylacetylene and two molecular proportions of methyl fumarate were heated under nitrogen in a sealed tube at 175 C. for 24 hours, and then subjected to vacuum distillation, which resulted in a viscous, amber residue. This residue was crystallized from methanol, yielding the product:

The product has a melting point of 11l.6 112.6 C. and an empiric composition of CuHuOa. Absorption spectrum data indicates the presence of two conjugated double bonds as shown.

Example 7.trans-6,7-trans-11,IZ-Tetracarboethozcy-S (14) ,Q-chrysitadiene One molecular proportion of dicyclohexenylacetylene and two molecular proportions of ethyl fumarate were heated under carbon dioxide in a sealed tube at 175 C. for seven hours. The product was subjected to vacuum distillation yielding a yellow viscous residue. The residue was crystallized from ethanol-water, forming the product:

cmooo COOCIHJ CaHsOO C a CH: J] H:

on, c c Cl 43g: li CH: 3Q 000cm.

The product has the empiric composition Gaol-1420a and absorption spectrum data indicates the presence of two conjugated double bonds spread over two rings. The melting point is 90-9l C.

Example 8.-3-Methoa:y-trans-6,7-trans-11,12-

tetracarbomethoxy-8-(14) ,Q-steTadiene One molecular proportion of 4-methoxyclohexenylcyclopentenylacetylene and two molecular proportions of methyl fumarate were heated and subjected to vacuum distillation as described in Example 6. The resulting viscous, amber residue was purified by distillation at 10- mm. and about 150 C. Analysis indicates the empiric formula 027K360, and observation of the absorption spectrum indicates the structural Example 9. Tetramethyl 1,6 dimethyl 5,6- propano 2,3,4,6,7,8 hexahydronaphthalene- 3,4;7,8-trans, trans-tetracarbozylate One molecular proportion of isopropenyl-omethyl-cyclopentenylacetylene and two molecular proportions of methyl fumarate were heated and subjected to vacuum distillation as described in Example 6. The product was purified for analysis by distillation at 10=1omm. and -112 C. It has the empiric formula 0221123011 and analogy with the previous example indicates the structural formula:

Having thus described my invention, I claim:

1. The 6a-methyltetradecahydrochrysene-5,6,- l1,l2-tetracarboxylic-5,6 11,12-dianhydride, having substantially the structure:

2. The process of manufacturing a non-bemzenoid fused polycyclic compound containing a 1,3-diene system, which comprises reacting one mole of a 1,5-diene-3-yne with two moles of a compound of the group consisting of anhydrides, esters, and acids containing the atomic grouping O-COCH=CH-CO- by heating said reactants in a closed vessel in the absence of any solvent until the fused polycyclic compound is formed, and then isolating said compound with non-reactive solvents.

3. The process of manufacturing a non-benzenoid fused polycyclic compound containing a 1,3-diene system, which comprises reacting one mole of a 1,5-diene-3-yne with two moles of an alkyl fumarate by heating said reactants in a closed vessel in the absence of any solvent until the fused polycyclic compound is formed, and then isolating said compound with non-reactive solvents.

4. The process of manufacturing a non-benzenoid fused polycyclic compound containing a :14 ass-moo '1,8-diene system, which comprises reacting one mole of a 1,5-diene-8-yne with two moles of methyl fumarate by heating said reactants in a closed vessel in the absence of any solvent until the fused polycyclic compound is formed. and I then isolating said compound with non-reactive solvents.

5. The process of manufacturing the compound 8a methyl-1 ,2,8,4,5,6,6a,'|,8,9,10,11,12,12a tetradecahydrochrysene-5,6,11,12-tetracarboxylic-5,6; 1

11,12-dianhydride, which comprises reacting one mole of cyclohexenyl-(Z-methvlcyclohexenyl)- acetylene with two moles of maleic anhydride by heating said reactants in a closed vessel in the absence of any solvent at a temperature of about 1s 150 C. until the compound is formed, and then isolating said compound with non-reactive solvents.

6. The process of manufacturing the compound 1-methyl-5,6-propano-2,3,4,6,7,8-hexahyan dronaphthalene 3,4,73-tetracarboxylic -8,4;7,8- dianhydride, which comprises reacting one mole of cyclopentenylisopropenylacetylene with two moles of maleic anhydride by heating said reactants in an open vessel while excluding air in "a the absence of any solvent at a temperature of about 155 C. until the compound is formed, and then recovering said compound.

'7. The process of manufacturing the compound trans-6,7-trans-ll,12-tetracarb0meth0w- 10 8(14),9-chrysitadiene. which comprises reacting one mole of dicyclohexenylacetylene with two moles of methyl fmnarate by heating said reactantsinaclosedvesselintheabsence ofany said fused polycyclic compound is formed, andthen isolating said compound with non-reactive solvents.

9. The process of manufacturing a non-ben- 'zenoid fused polycycliccompound containing a 1,3-diene system, which comprises reacting one mole of a 1,5-diene-3-yne with two' moles of maleic anhydride by heating said reactantsin a closed vessel in the absence of anysolvent at a temperature of about 130' to 175' C. until said fused polycyclic compound is formed, and then isolating said compound with non-reactive solvents.

. 10. The process of manufacturing a non-benaenoid fused polycyclic compound containing a 1,3-diene system which comprises reacting one mole of a 1,5-diene-3-yne with two moles of maleic anhydride by heating said reactants in a closed vessel in the absence of any solvent at a temperature of about 130 to 175' C. for from one to four hours, whereby said fused po ycyclic compound is formed. and then isolating said compound with. non-reactive solvents.

LIWIB W. BU'I'Z. 

